庆大霉素肾中毒大鼠肾皮质线粒体、溶酶体损伤机理的研究

Study of gentamicin-induced mitochondrial and lysosomal damages in renal cortex in rats

采用庆大霉素（ＧＭ）肾中毒大鼠模型，观察肾皮质线粒体、溶酶体膜流动性及其标志酶玻珀酸脱氢酶（ＳＤＨ）、酸性磷酸酶（ＡＣＰ）活性的变化以及形态学改变。ＧＭ组０．５ｈ，线粒体、溶酶体膜流动性非常显著下降，并随时间进行性下降；ＳＤＨ及ＡＣＰ酶活性亦同时发生相应变化；电镜下，ＧＭ组０．５ｈ，近端肾小管上皮细胞未见明显异常，１ｈ后线粒体及溶酶体出现明显损伤征象。结果提示，ＧＭ肾中毒时，肾皮质线粒体、溶酶体膜流动下降是其肾毒性发病机理的重要环节。

The changes of membrane fluidity of the mitochondria and lysosomes in the renal cortex,the activities of their marker enzymes,succinate dehydrogenase(SDH)and acid phosphatase(ACP),and the morphological changes were studied in rats with gentamicin(GM)-induced nephrotoxicity. It was found that the membrane fluidity of mitochondria and lysosomes in the renal cortex was very significantly decreased 0.5 hour after the administration of GM and it kept on decreasing along with the elapse of time.Corresponding changes of the activities of SDH and ACP were observed simultaneusly.Under electron microscopy,no obvious changes of the epithelial cells of the proximal tubules were observed 0.5 hour after GM administration but severe mitochondrial and lysosomal damages were found in the lst hour. These findings suggest that the changes of the membrane fluidity of the mitochondria and lysosomes in the renal cortex may be the important cause of the damages of the organelles in GM-induced nephrotoxicity.